Identification of sequence variations in the apolipoprotein A2 gene and their relationship with serum high-density lipoprotein cholesterol levels

Background: Apolipoprotein A2 [APOA2] is the second major apolipoprotein of the high-density lipoprotein cholesterol [HDL-C]. The study aim was to identify APOA2 gene variation in individuals within two extreme tails of HDL-C levels and its relationship with HDL-C level

Methods: This cross-sectional survey was conducted on participants from Tehran Glucose and Lipid Study [TLGS] at Research Institute for Endocrine Sciences, Tehran, Iran from April 2012 to February 2013. In total, 79 individuals with extreme low HDL-C levels [/=95[th] percentile for age and gender] were selected. Variants were identified using DNA amplification and direct sequencing

Results: Screen of all exons and the core promoter region of APOA2 gene identified nine single nucleotide substitutions and one microsatellite; five of which were known and four were new variants. Of these nine variants, two were common tag single nucleotide polymorphisms [SNPs] and seven were rare SNPs. Both exonic substitutions were missense mutations and caused an amino acid change. There was a significant association between the new missense mutation [variant Chr.1:16119226, Ala98Pro] and HDL-C level

Conclusion: None of two common tag SNPs of rs6413453 and rs5082 contributes to the HDL-C trait in Iranian population, but a new missense mutation in APOA2 in our population has a significant association with HDL-C

Association of lecithin cholesterol acyltransferase rs5923 polymorphism in Iranian individuals with extremely low high-density lipoprotein cholesterol: Tehran lipid and glucose study

The serum concentration of high-density lipoprotein cholesterol [HDL-C] is one of the important heritable risk factors for cardiovascular disease and is a target for therapeutic intervention. In this study, we aimed to evaluate the effects of lecithin cholesterol acyltransferase [LCAT] gene polymorphism rs5923 on LCAT enzyme activity and serum HDL-C concentration. The study population was selected from consecutive individuals with HDL-C /= 95[th] percentile [n = 57] who had participated in the Tehran Lipid and Glucose Study. The rs5923 polymorphism was genotyped using direct sequencing. LCAT activity was measured by fluorometric assay kit, and lipid concentrations were measured using the enzymatic colorimetric method. The genotype frequencies were significantly different between the high HDL-C group [CC 94.7%, CT 5.3%] and the low HDL-C group [CC 83.6%, CT 16.4%] [P = 0.048]. The Tallele frequencies in subjects with low and high HDL-C were 0.082 and 0.026, respectively [P = 0.16]. The association of the single-nucleotide polymorphism rs5923 with low HDL-C was not statistically significant after adjustment for age, sex, and BMI [odd ratio = 2.65, 95% confidence interval = 0.32-21.5, P = 0.36, regression logistic analysis]. Also, the effects of LCAT enzyme activity did not depend on the HDL-C level [P = 0.24]. rs5923 polymorphism is not associated with low HDL-C levels in Iranian population

[Genetic association of selected microsatellite with some metabolic syndrome components in Iranian Fars and Azari families]

Family base association test [FBAT] is widely used in study of genetic association of allele of genetic markers and different phenotype for locating genes locus. The present study attempted to investigate the genetic association of some candidate microsatellites with HDL-C, triglyceride, and waist in order to find chromosomal area locus of effective genes in metabolic syndromes in Persian and Azari people of Iran. in this study 107 families were selected from participants in Tehran Lipid and Glucose Study. Each family had at least one member with metabolic syndrome [according to ATP III] and at least two members with reduced HDL-C level. The genetic association of HDL-C, triglyceride, and waist with some candidate microsatellites in chromosome 8, 11, 12, and 16 was studied using FBAT. the data covered 107 families consisting of 483 individuals. For Persian individuals, study of Chromosome 8 revealed significant association between D8S514 and HDL-C and between D8S1743 and triglyceride [P<0.05]. For Azari individuals, association of D8S1132 and D8S1743 in Chromosome 8 to HDL-C was significant [P<0.05]. FBAT is robust against confounders such as misspecification of genetic models and population stratification. By finding microsatellites affecting HDL-C, triglyceride, and waist, the results found in this study may be helpful in determining predisposing genes in metabolic syndrome.

[Thyroid peroxidase gene polymorphisms and anti-TPO level in Tehranian adults]

TPO gene variations are one of the causes of thyroid autoimmune diseases. The aim of this study was to examine the association between the T1936C, T2229C and A2257C SNPs [single nucleotide polymorphisms]of the TPO gene and Anti-TPO level. In this case-control study, 188 individuals [86 males and 102 females], aged 20-80 years, were randomly selected from the Tehran Lipid and Glucose Study population [TLGS]. A2257C and T2229C SNPs were detected with RFLP by use of BsrI and Eco57I as restrictive enzymes respectively, while the T1936C SNP was determined with ARMS-PCR. In the presence of the C allele of T1936C, Anti-TPO level was significantly increased [CC: 238 +/- 43.3, CT: 47.7 +/- 15.9, TT: 74.1 +/- 11.3 IU/L; p 0.002]; however, it disappeared after adjustment for sex and age [p 0.059]. No significant difference, before and after adjustment, was found in Anti-TPO level in the presence of T2229C SNP [CC: 129.1 +/- 24.5, CT: 43.5 +/- 12.6, TT: 126.5 +/- 13.8 IU/L; p 0.196]. The association of A2257C with Anti-TPO level was only significant after adjustment for sex and age [p 0.007],and between the ATC ,CTT haplotypes and Anti-TPO level ,the association was significant [p 0.023, 0.021]; however, the association it was dominant between CTT and anti-TPO concentration was significant only after adjustment for sex [p 0.014]. The result of this study, showed age and sex as potential confounders which could modify the association between TPO polymorphisms and Anti-TPO level in a Tehranian population

[Association between TNF-alpha promoter G-308A and G-238A polymorphisms and obesity in Tehran lipid glucose study population]

Tumor necrosis factor-alpha [TNF-alpha] is expressed primarily in adipocytes and elevated levels of this cytokine have been linked to obesity and insulin resistance. Therefore, we examined the relationship between the G-308A and G-238A polymorphisms of TNF-alpha gene promoter variants and obesity in an Iranian population. Subjects of the Tehran Lipid and Glucose Study classified into two age groups under and above 18. Adults classified in three groups according to their body mass index and less than 18 years old subjects classified in two groups [under 85th percentile for their age and sex and above 85th percentile]. 244 persons were selected to examine -308 site and 239 persons were selected to examine -238 site. The mentioned polymorphisms were examined with PCR and RFLP methods. The allele frequency of TNF-alpha polymorphism was in the Hardy Weinberg equilibrium and there was no relation between BMI and the frequency of this allele. No association between G-308A and G-238A TNF-alpha promoter polymorphisms and obesity could probably indicate that it is not an important risk factor for obesity and consequently for cardiovascular disease

Analyzing of multivariate two levels Haseman-Elston regression and its application in genetic linkage of HDL-C, triglycerides and waist in 91 Iranian families with metabolic syndrome

Metabolic syndrome is a complex trait and its prevalence is 32% in Iranian population. The present study was conducted to find chromosomal area locus of HDL-C, triglycerides and waist with microsatellites and multivariate two level Haseman-Elston regressions in Iranian families with metabolic syndrome. 91 Iranian families [493 people] with at least one member with metabolic syndrome were selected from database of TLGS. We performed the Fragment Analysis technique to reproduce 12 different pieces from 4 chromosomal areas and to identify loci related to metabolic syndrome; both single and multi variable two level Haseman-Elston regression methods were used for traits of triglycerides, high-density lipoprotein and waist. We performed three single variable models, three double variable models and one triple variable model of these traits. 91 Iranian familes included 493 people, 234 males and 259 females. In single variable models: genetic linkage of HDL-C was significant with D11S1998 marker; genetic linkage of triglycerides was significant with Dl IS 1934 and D12S1632 markers. In double variable models genetic linkage of HDL-C and triglyceride, HDL-C and waist was significant with Dl IS 1998 marker and the genetic linkage of HDL-C and triglyceride, triglyceride and waist was significant with D8S1743 and D11S934 marker. In triple variable model genetic linkage of HDL-C, triglyceride and waist was significant with D8S1743 marker. These results showed when a trait is common in different models; the linked markers of them are also common. We concluded that the multivariate methods can detect linked loci of mixed disease better than single variable models and these results are useful for more future studies in Iranian population